Progressive systemic sclerosis (PSS) commonly involves the esophagus. Dysphagia and heartburn are the most common esophageal symptoms. In this study we evaluated the relationship between esophageal symptoms and esophago-gastric motility. On esophageal manometry, loss of peristalsis, peristaltic contraction amplitude of distal esophagus less than 30mmHg and decreased LES pressure were critical for esophageal symptoms. The degree of symptoms correlated to esophageal dysmotility. The gastric emptying in PSS patients was delayed, but there was no significant difference in gastric emptying between the patients with and without reflux esophagitis. Esophageal dysmotility is considered to be much resposible for the reflux esophagitis in PSS patients than gastric emptying.
The action of dopamine (DA, 10μg/kg/min) on pentagastrin (16μg/kg/hr) stimulated gastric acid secretion was studied by use of Ghosh-Schild's rats. DA suppressed pentagastrin-stimulated gastric acid secretion 44.6 percent compared with the level before administration. This decrease in acid was inhibited by pretreatment with β1 and β1+β2 blockers and pretreatment with DA1+DA2 and DA1antagonists. The gastric acid secretion with DA1 agonist decreased 36.4 percent from the level at the time of pentagastrin administration. This decrease was inhibited by pretreatment with β1 blocker, but suppression of gastric acid secretion by β1+β2 stimulator was not inhibited by pretreatment with DA1antagonist. These results suggest that DA stimulated β1, adrenalin receptor via DA1 receptor and thereby suppresses pentagastrin-stimulated agstric acid secretion.
The mechanism of cytoprotection by prostaglandins (PGs) is still unknown, although many hypotheses have been proposed. We postulated a hypothesis that increased gastric content and thickened mucus gel layer by PGs may protect the gastric mucosa against damage from necrotizing agents. Two series of experiments were performed on Wistar male rats, weighing 250-300g. (1) 16, 16-dimethyl prosaglandin E2 (dmPGE2) in dosis of 20μg/kg was given orogastrically. Fifteen minutes later, the stomachs were emptied and/or the mucus gel layer removed, and several concentration of ethanol applied. After ten minutes, the stomachs were removed and lesions of the gastric mucosae were evaluated macroscopically and histologically. (2) Volume and pH of the gastric content and mucus thickness were measured 15 minutes after dmPGE2 administration. DmPGE2 did not protect the gastric mucosa against 40% ethanol in the emptied stomach. This agent had no cytoprotective action on the emptied and mucus gel-removed stomach in 30% ethanol application. These results had no significant difference with control group (saline 1ml p.o.) about the extent of erosin. In histological study of the erosive region by scanning and light microscopy, we also found no differences in the depth of erosion between dmPGE2 group and control. In addition, dmPGE2increased the gastric volume and mucus thickness significantly. These data suggest that following two effects by PGs play major role in cytoprotection of the gastric mucosa; (1) dilution of necrotizing agents by increased gastric content, and (2) thickening of the mucus gel layer.
Tissue kallikrain could be specifically demonstrated in the human gastric mucosa using sandwich-type enzyme-linked immunosorbent assay. Eighty-five patients with chronic gastritis were then studied to investigate the relationship of tissue kallikrein to endoscopic and pathologic findings. The endoscopic Congo red method was used to classify the atrophic pattern of each patients gastric mucosa into the normal, closed or open type. Tissue kallikrein increased significantly in the closed type compared with the normal type (P<0.01) and in the open type compared with the closed type (P<0.001). Pathological findings were classified into three groups: (A) normal surface epithelium, with slight infiltration by inflammatory cells; (B) atrophic surface epithelium, with marked infiltration by inflammatory cells; and (C) atrophic surface epithelium, with marked infiltration by inflmmatory cells and intesinal metaplasia. Tissue kallikrein significantly increased in the B group compared with the A group (P<0.01) and in the C group compared with the B group (P<0.001). Tissue kallikrein markedly increased with the appearance of intestinal metaplasia in the open type rather than in the closed type. An immunohistological study demonstrated that tissue kallikrein was present in the cells showing intestinal metaplasia and goblet cells. These findings suggest that chronic gastritis is a process of reconstruction of gastric mucosa.
Oxyradicals of neutrophils are supposed to play a role in the formation of gastric mucosal injury induced by ischemia-reinfusion (I-R). Recently, platelet-activating factor (PAF) is suggested to be involved in the I-R injury as one of chemical mediators since this substance may be produced in hypoxic tissue. stimulating oxyradical generation of neutropils. In the present study, using CV-3988, a PAF antagonist, the severity of gastric mucosal damage and chemiluminescence (CL) activity of neutrophils of circulating blood were measured to evaluate the role of PAF in the I-R injury. SD rats fasted overnight were anesthetized and instilled 0.1N HCl into the stomach. Rats were then subjected to reduction of blood pressure to 20-30mmHg for 20min by bleeding followed by reinfusion of shed blood for 20min. Two groups of rats each received 10mg/kg CV-3988 (PAF-A grup) or saline (I-R group) i.v. 5min prior to bleeding. After killing rats, the area of gross gastric lesions and the index of histologic damage were assessed. In separate PAF-A and I-R groups of rats, and control rats received saline i.v. and no hypotension, blood samples were collected from the portal vein and the abdominal aorta 45min after acid instillation. Luminol-dependent CL stimulated by PMA of blood samples was measured using the photometer Monolight 401. CL activity was expressed as [peak CL/neutrophils number]. The area of gross lesions was significantly smaller in the PAF-A group than in the I-R group in the corpus (120 vs. 363mm2), but not in the antrum (10 vs. 10mm2). However, the index of histologic damage both in the corpus and antrum was significantly smaller in the PAF-A group than in the I-R group (corpus, 0.9 vs. 1.8; antrum, 0.9 vs. 2.0). CL activity of neutrophils either from the portal vein or the aorta was significantly greater in the I-R group than in PAF-A and control group groups (I-R, control, PAF-A: protal, 17.3, 6.6, 5.3×10-4 RLU; aorta, 40, 8.1, 9.1×10-4 RLU). PAF plays in part a role for the formation of ischemia-reinfusion injury in the rat stomach. Oxyradicals generation stimulated by PAF of neutrophils may be involved in this mechanism.
The role of vagus nerve for release of gastrin, secretin and somatostatin in dogs was studied. Bilateral cervical vagotomy and electric vagal stimulation (25V 0.5msec 10Hz) were performed and blodlevels of gut hormones were measured. After vagotomy, blood levels of gastrin, secretin and somatostatin did not change. The electric vagal stimulation elevated blood level of gastrin. Atropine and hexamethonium inhibited the elevation. The electric vagal stimulation did not change blood levels of secretin and somatostatin. In conclusion, vagal stimulation releases gastrin into blood ciruclaion depending on The chlinergic mechanism.
Activities of cathepsin B, cathepsin L, and plasminogen activators (urinary type plasminogen activator and tissue type plasminogen activator) were assayed in homogenates of cancer tissue, normal tissue closely surrounding the cancer tissue, and normal tissue distant from the cancer tissue from 30 patients undergoing surgery for gastric cancers and 10 patients undergong surgery for colon cancers. Activities of those proteases were also assayed in homogenates of adenoma tissue from 10 patients undergoing polypectomy for colon polyps. In the gastric cancer tissue homogenates, the activities of cathepsin B, cathepsin L and tissue type plasminogen activator were significantly higher than in normal tissues. By contast, the activities of urinary type plasminogen activator of gastric cancer tissues were significantly lower than normal tissues. In the colon cancer tussue homogenates, the activities of cathepsin, B, cathepsin L, and urinary type plasminogen activator were significantly higher than in normal tissues. On the other hand, the activities of tissue type plasminogen activator of cancer tissues were significantly lower than normal tissues. But there were no significant differences in the activities of plasminogen activators between the cancer tissues and adenoma tissues. These results suggest that cathepsin B and cathepsin L play an important role in gastric and colon cancer proliferation and evolution, although the roles of plasminogen activators in gastric and colon cancer proliferation and evolution and in the colon adenoma-carcinoma sequence are still unknown.
To elucidate the cell biological significance of ras oncogene, the expression of ras-p21 was analyzed in 53 cases of liver tissues including 34 cases of hepatocellular carcinoma (HCC), by using immunohistochemical method. In result, 22 (65%) cases of 34 HCC and 34 (79%) cases of 43 liver cirrhosis were positive for p21, whereas all of chronic hepatitis and normal livers were negative. Especially, comparative study between the expression of p21 and clinicopathological background of HCC revealed that p21 was prominently expressed in well diferentiated form, nodular type, small liver cancer, and the cases showing AFP levels below 400ng/ml. From these reuslts, it was indicated that ras oncogene might play an important role in malignant transformation of hepatocytes or differentiation of HCC.
This study was performed in order to elucidate the mechanisms of systemic endotoxemia in liver cirrhosis. For this purpose, the method of measuring biliary endotoxin was established. Endotoxin levels between in the bile and in the plasma in cirrhosis were compared using a modified method of chromogenic quantitative endotoxin assay in an attempt to clarify liver function of clearing portal endotoxin originated from the gut. And functional activities of the reticuloendothelial system were also examined by radioassay with 59Fe-labelled iron-chondroitin sulfate colloid and by enzymohistochemistry of acid phosphatase. Both the plasma and biliary endotoxin levels in liver cirrhosis were significantly higher, compared to those in control. The functional activities of the reticuloendothelial system, particularly of the Kupffer cells, were decreased in liver cirrhosis. These data provide evidence that in liver cirrhosis systemic endotoxemia is mainly due to a decrease of functional activities of Kupffer cells. On the other hand, the excretion of endotoxin into the bile is increased, compensating the decreased functional activities of Kupffer cells. This implies that the uptake of endotoxin and its excretion into the bile by hepatocytes might be one of the mechanisms of clearing excess endotoxin in the plasma in liver cirrhosis. This study also drows the importance of measurements of endotoxin levels in the bile in liver diseases.